Phenyl and alkyleneamino substituted
imidazolidinones and salts thereof



United States Patent 3,196,152 PHENYL AND ALKYLENEAMINO SUBSTITUTEDIMIDAZOLIDINORES AND SALTS THEREOF William B. Wright, Jr., WoodciifiLake, N.J., and Herbert J. Brabander, Pearl River, N.Y., assignors toAmerican 'Cyanarnid Company, Stamford, Conn., a corporation of MaineNoDrawing. Filed Sept. 28, 1962, Ser. No. 227,078

- 19 Claims. (Ci. 26tl-- 247.2)

This is a continuation-in-part of application Serial No. 147,203 filedOctober 24, 1961, now abandoned.

This invention relates to new organic compounds. More particularly, itrelates to substituted imidazolidinones and imidazolidinethiones andmethods of preparing the same.

'In. the prior art, imidazolidinones and im-idazolidinethiones are knownwhich have aryl groups on one or both of the nitrogen atoms, however,none have been found which contain an aryl group on one nitrogen andsubstituted alkylene amine groups on the other nitrogen of theheterccyclic basic ring structure.

We have now found that compounds having the following structure arehighly active tranquilizers:

wherein R is a hydrogen, halogen, lower alkyl, lower alkoxy,trifiuoromethyl, lower alkylthio, lower alkylsulfonyl, lower alkanoyl,hydroxy or aralkoxy group; R and R are hydrogen, lower alkyl, alkenyl,propargyl, cycloalkyl, aralkyl, or when taken together with the nitrogenform pyrrolidino, lower alkylpyrrolidino, piperidino, loweralkylpiperidino, hexarnethyleneimino, morpholino, lower alkylmorpholino,lower alkylpiperazino, hydroxylower alkylpiperazino and loweralkanoyloxydoweralkylpiperazino groups; Y is oxygen or sulfur; n is aninteger frorn 2 to 4 and A and'B are hydrogen or lower alkyl groups andthe acid addition salts of the above compounds. The compounds of thepresent invention are, in general, liquids at room temperature as theirfree bases. As such, they are relatively insoluble in water but aresoluble in or miscible with most organic solvents such as, for example,lower alkyl alcohols, esters, acetone, chloroform and the like. Thesecompounds form acid addition salts with strong acids such ashydrochloric acid, sulfuric acid, perchloric .acid and the like. Thesesalts are, in general, soluble in water, methanol, ethanol, etc. butrelatively insoluble in benzene, ether, petroleum-ether and the like.

The present compounds have been tested and found to have tranquilizingproperties which shown a desirably wide spread between the dosesproducing sedative action and toxic symptoms such asparalysisorlethality. The tranquilizer meprobamate has a markedly reduced rangebetween the sedative and paralytic doses, and is inferior to the presentcompounds in this respect.

3,196,152 Patented July 20, 1965 The compounds of this invention may beprepared by the following method which has been found most desirable.

wherein R R R A, B, and It are as defined above and X is a reactivehalogen or arylsulfonyloxy radical. The imidazolidinone is dissolved inan inert solvent such as, for example, diethylenegylcol dimethyl ether(diglyme) and reacted with a' condensing agent such as sodiumhydride andthen; with an appropriate aminoalkyl halide. The reaction is bestcarried out at temperatures in the range of 30-200 C. for a period offrom 30*min'utes to 4 hours. 'The'produ'ct can be recovered by methodswell known in the art and described hereinafter in the examples.

The compounds of the present invention can also be preparedbyseveral'other methods, one group of which have in common the cyclizationof a'straight chain'cornpound to produce the desired imidazolidinonering struc tote with the substituents present thereon; One method founduseful in producing the compounds o'f'the present invention is thecyclization of substituted carbanilates which can be illustrated by thefollowing reacti n:

b -o CzH5 1 RaRzN C n 2 NH-CHCHN i mmucun lr n -Q 9 in which R R R A, Band n are defiined above. The starting material, namely, N-substituted(aminoalkyl) ureas can be prepared by the various methods described inthe literature.

Other methods of preparing the compounds of the present invention can beillustrated as follows:

in which R R R A, B and n are as defined above.

The various cyclization reactions illustrated above can 'be carried out,for example, by heating the reagents alone in which R R R A, B and n areas defined hereinbefore.

A still further method for preparing the compounds of the presentinvention can be illustrated as follows:

wherein R R R A, B and n are as defined above and X is a reactivehalogen or arylsulfonyloxy radical. The reaction conditions do notappear to be critical. The

alkylating agent (containing X) is reacted with the amine (R R NI-I) inexcess or in the presence of an acid acceptor such as sodium orpotassium carbonate, sodium hydroxide, pyridine and the like. Thereaction is preferably carried out in the presence of an excess of theamine or in a solvent such as benzene, toluene, ethanol, acetone and thelike. The reaction is best carried out within the range of about 20 C.to about C. for a period from about 30 minutes to several hours. Theproduct can be recovered by methods well known in the art and asdescribed hereinafter in the examples.

The corresponding imidazolidinethiones are also a part of this inventionand in some cases they can be prepared by processes similar to thosedescribed above. t is, however, preferable to prepare these compounds byspecial procedures, such as by the reaction of the imidazolidinone withphosphorus pentasulfide as described hereinafter in the examples.

The products of the present invention as tranquilizers can beincorporated in various pharmaceutical forms such as tablets, capsules,pills and so forth, for immediate or sustained release, by combiningwith suitable carriers. They may be in the form of dosage units for asingle therapeutic dose or in small units for multiple dosages or inlarger units for division into single doses. Obviously, in addition tothe therapeutic tranquilizing compound there may be present excipients,binders, fillers and other therapeutically inert ingredients necessaryin the formulation of the desired pharmaceutical preparation.

The following specific examples illustrate the preparation ofrepresentative compounds of the present invention. Parts are by weightunless otherwise indicated.

EXAMPLE 1 Preparation ofJ-(m-chlorophenyl)-3-(S-dimethylaminopropyl)-2-imidazolidinonehydrochloride A solution of 3 parts of1-(m-chlorophenyl).-2-imidazolidinone in 30 parts of diglyme is addeddropwise to a slurry of 0.7 part of 50% sodium hydride (in mineral oil)in 50 parts of diglyme. The reaction mixture is stirred for one hour anda solution of 1.8 parts of 3-dimethylarninopropyl chloride in 20 partsof diglyme is added. The reaction mixture is heated at refluxtemperature for 3 hours, cooled, treated with 0.8 part of methanol, andfiltered. The mother liquor is concentrated under reduced pressure toremove the solvent and the residue is dissolved in ether. Dry hydrogenchloride gas is bubbled thru the solution and the salt which forms isseparated and washed with ether. The salt is recrystallized and theproduct l-(m-chlorophenyl)-3-(3-dimethylaminopropyl)-2-imidazolidinonehydrochloride melts at 174175 C. V

EXAMPLE 11 Preparation of 1-(ii-dimezhylaminopropfl)-3-phenyl-Zimidazolidinone A solution of 3 parts of 1-phenyl-2-imidazolidinone in50 parts of diglyme is added dropwise to a slurry of 0.84 part of 50%sodium hydride (in mineral oil) in 50 parts of diglyme. The reactionmixture is stirred for one hour, and a solution of 2.2 partsof3-dimethylaminopropyl chloride in 20 ml. of diglyme is added. Thereaction mixture isheated at reflux temperature for 3 /2 hours, cooledand filtered. The mother liquor is concen rated under reduced pressureto remove the solvent and the residue is triturated with hexane.Crystals of unreacted starting material separate and are filtered 01f.The filtrate is concentrated to an oil. The oil is dissolvedain etherand 10 parts of 1.7 N ethanolic hydrogen chloride is added. An oilseparates and is washed With ether to remove impurities. Crystallizationoccurs.' T he hygroscopic crystals. are dissolved in water and treatedwith aqueous sodium hydroxide. The mixture is extracted with ether.Evap-- oration of the ether layer results in analytically pure 1-(3-dimethylaminopropyl)-3-phenyl-2-imidazolidinone.

The above compound is obtained when 4-methyl-3- phenyl-2-imidazolidinoneis substituted for l-phenyl-Z- iniidazolidinone in the proceduredescribed in Example II.

EXAMPLE IV 3-(S-diinezhyZaminopropyl)-4 methyl 1-phenyl-Z-imidazolidinone The above compound is obtained when 4-methyl-1-phenyl-Z-imidazolidinone is substituted for 1-phenyl-2- imidazolidinonein the process of Example II.

EXAMPLE v Preparation of 1 -pheny [-3- (Z-pi peridinoethyl -2-im id(120- lidirzone hydrochloride A solution of 3 parts of 1-phenyl-2imidazolidinone in 50 parts of diglyrne is added dropwise to a slurry of0.84 part of 50% sodium hydride (in mineral oil) in 50 parts 'ofdiglyme. The reaction mixture is stirred for one hour, and as'olution of2.7 parts of 2-piperidinoethyl chloride in 50 parts of other is added.The reaction mixture is heated at reflux for 3 hours, cooler, andfiltered. The filtrate is concentrated to remove the solvents. Theresidue is mixed with 7 parts of N hydrochloric acid and parts of Waterand the mixture is extracted with chloroform to remove unwantedimpurities. The aqueous layer is made alkaline and the1-phenyl-3-(2-piperidinoethyl)- 2-imidazolidinone is extracted intoether. 'Addition of ethanolic hydrogen chloride results in precipitationof the hydrochloride salt, melting point 218-219 C. afterrecrystallization.

Preparation of EXAMPLE VI Preparation ofJ-(p-ethylphenyl)-3-(Z-piperidinoethyl)- 2-in idazolidinonehydrochloride The above compound is obtained whenl-(p-ethylphenyl)-2-imidazolidinone is substituted for 1-phenyl-2-imidazolidinone in the procedure of'Example V;

EXAMPLE VII Preparation of l-(2-hexamethyleniminoethyl)-3-phenyl-Z-irnidazolidirtone hydrochloride The above compound is obtained when2-hexamethyleniminoethyl chlorideis substituted for 2-piperidinoethylchloride in the process of Example V.

EXAMPLE VIII Preparation of1-phenyl-3-(Z-pyrrolidinoethyl)-2-imidazolidinone hydrochloride Theabove compound is obtained when 2-pyrrolidino ethyl chloride issubstituted for 2-piperidinoethyl chloride in the procedure of ExampleV. The compound has the melting point 220-222" C.

' EXAMPLE 1x Preparation of 1-(tn-chlorophenyl)3-(2-piperidinoethyl) i rZJtnidazolidinone hydrochloride The above compound, melting point212-214 C. is obtained when Z-piperidinoethyl chloride is substitutedfor dimethylaminopropyl chloride in the process of Example I. l

XA PL X Preparation of 1-(Z-benzylmethylaminoethyl)-5 (mclzlorophenyl)2-irnidazolidinonehydrochloride The above compound, melting pointl8819() C., is obtained when 2-benzylmethylaminoethyl chloride issubstitut'ed for 3-dimethylaminopropyl chloride in the process ofExample I.

6 EXAMPLE x1 Preparation of 1- (m-chlorophenyl) -3-(Z-dimethylaminoethyl )-2-imidazolidinone hydrochloride The abovecompound, melting point 217-2l9 C., is obtained whenZ-dimethylarninoethyl chloride: is substituted for S-dimethylaminopropylchloride in the process of Example I.

EXAMPLE XII Preparation of 1 -(m-chlorophenyl) -3- [3 (4-methyl-1-piperazinyl) propyl]-2-imidaz0lidinone dihydrochloride The abovecompound, melting point 277278 C., is obtained when3-(4-methyl-1-piperazinyl)propyl chloride is substituted for3-dimethylarninopropyl chloride in the process of Example I.

EXAMPLE XIII Preparation of 1- (Z-diethylaminoethyl)-3-(p-eth0xyphen'yfi) -2-imidaz0lidinone A solution of 3.8 parts ofl-(p-ethoxyphenyl)-2-imid azolidinone in 50 parts of diglyme is addeddropwise to'a slurry of 0.84 part of 50% sodium hydride (in mineral oil)in 50 parts of diglyme. The reaction mixture is stirred for one houranda solution of 2.5 parts of 2-diethylaminoethyl chloride in 50 partsof other is added. The reaction mixture is heated at reflux temperaturefor 3 hours, cooled and filtered. The filtrate is concentrated to removethe solvents. The residue is mixed With 7 parts of 5 N hydrochloric acidand 25 parts of Water and the mixture is extracted with chloroform toremove unwanted impurities. The aqueous layer is made alkaline. The1-(Z-diethylaminoethyl)-3-(p-ethoxyphenyl) 2 imidaz olidinone isextracted into ether and isolated by concentration of the ethersolution.

EXAMPLE XIV Preparation of1-(m-trifllloromethylphenyl)-3-(2-dimethylaminoetltyl)-2-imidazolidinone hydrochloride The above compound, melting point168-170 C., is obtained when1-(m-trifluoromethylphenyl)-2-imidazolidinone is substituted for1-phenyl-2-imidazolidinone and Z-dimethylaminoethyl chloride issubstituted for Z-piperidinoethyl chloride in the process of Example V.

EXAMPLE xv Preparation of 1 -[3-(4-methyl-I -pi perazinyl pro pyl]-3-phenyZ-Z-imidazolidinone dihydroch loride A mixture of 6.2 parts of1-(rn-chlorophenyl)-3[3-(4- methyl-l -piperazinyl propyl]-2-imidazolidinone dihydrochloride, 100 parts of ethanol and 1 part of10% palladium on carbon catalyst is placed in a Parr hydrogenator underabout 45 p.s.i. of hydrogen pressure, and shaken for three hours. Thereaction mixture is filtered and the mother liquor is concentrated toremove solvents.

The residue is triturated with ether and the crystalline product isfiltered off. Analytically pure 1-[3-(4-rnethyll-pipera'z'inyl]-3-phenyl-2 imidazolidinone dihydrochloride, melting point 278-280" C,is obtained by recrystallization.

EXAMPLE XVI Preparation of I-(Z-methylaminoethyl)-3-phenyl-2-imidazolidinone hydrochloride The above compound, melting point 221-223"C., is obtained when 1 (2 benzylmethylaminoethyl) 3 (mchlorophenyl)-2-imidazolidinone hydrochloride is hydrogenated accordingto the procedure of Example XV.

Ti methylarninoethyl)-2-imidazolidinone hydrochloride is substituted for1-(m-chlorophenyl)-3-[3-(4-methyl-1- piperazinyl)-propyl]-2-imidazolidinone dihydrochloride in the process of Example XV.

EXAMPLE XVIII Preparation of 1 (Z-dimethylaminoethyl) -3-phenyl-2imidazolidinone hydrochloride The above compound, melting point 149-l50C., is obtained when 1 (m chlorophenyl) 3 (2diethylaminoethyl)-2-imidazolidinone hydrochloride is substituted for 1(m chlorophenyl) 3 [3 (4 methyl 1- piperazinyl) propyl] 2imidazolidinone dihydrochlorride in the procedure of Example XV.

EXAMPLE XIX Preparation 1-(Z-ethylmethylaminoethyl)-3-phenyl-2-imidazolidinone hydrochloride When 1 (m chlorophenyl) 3 (2ethylmethylaminoethyl) 2 imidazolidinone hydrochloride is substitutedfor 1 (m chlorophenyl). 3 [3 (4 methyl- 1 piperazinyl) propyl] 2imidazolidinone dihydrochloride in the process of Example XV, the abovecompound, melting point 163-l64 (3., is obtained.

EXAMPLE XX Preparation of I-(m-chlorophenyl)-3-(2-diethylaminoethyl)-2imidazolidin0ne hydrochloride The above compound, melting point 144l45"C., is obtained when 2-diethylaminoethyl chloride is substituted for3-dimethylaminopropyl chloride in the procedure of Example I.

EXAMPLE XXI EXAMPLE XXII Preparation ofJ-(m-chlorophenyl)-3-(Z-pyrrolidinoethyl)-2-imidazolidinonehydrochloride When Z-pyrrolidinoethyl chloride is substituted for 3-dimethylaminopropyl chloride in the process of Example I, the abovecompound, melting point 19l-l92 C., is

isolated.

7 EXAMPLE XXIII Preparation ofl-(m-ehlorophenyl)-3-[2(Z-methylpyrrolidino)ethyl]-2-imidaz0lidinonehydrochloride The above compound is obtained when2-(2:methylpyrrolidino)ethyl chloride is substituted for3-d1methylaminopropyl chloride in the process of Example I.

EXAMPLE XXIV Preparation of l-(mchlorophenyl)-3-[2(2-methylpiperidino)ethyl]-2-imidazolidinorzehydrochloride The above compound is obtained when2-(2-methylpiperidino)ethyl chloride is substituted for 3-dimethy1-'aminopropyl chloride in the procedure of Example 1;

EXAMPLE XXV Preparation of1-(in-chlorophenyl)-3-(2-morpholinoethyl)-2-imidazolidinonehydrochloride When 2-morpholinoethyl chloride is. substituted for the3-dimethylaminopropyl chloride in the procedure of Example I, the abovecompound, melting point 2l9221 C., is obtained.

8 EXAMPLE XXVI Preparation 0 f 1 (p-chlorophenyl -3- (3-dim ethylaminopropyl -2imidaz0lidinone hydrochloride When1-(p-chlorophenyl)-2-imidazolidinone is substituted for thel-(m-chlorophenyl)-2-imidazolidinone in the procedure of Example I, theabove compound, melting point 177-178 C., is obtained.

EXAMPLE XXVII Preparation of 1-(m-bromophenyl)-3-(3-dimethylaminopropyl) -2-imidazolidinone hydrochloride The abovecompound, melting point 168169 C., is obtained whenl-(m-bromophenyl)-2-imidazolidinone is substituted for1-(rn-chlorophenyl)-2-imidazolidinone in the procedure of Example I.

EXAMPLE XXVIII Preparation of 1-(m-methylthiophenyl) -3 (diniethylaminopropyl -2 -im idazoli dinone hydrochloride The above compound, meltingpoint 144146 C., is obtained when 1-(methylthiophenyl)-2-imidazolidinoneis substituted for the l-(m-chlorophenyl)-2-imidazolidinone in theprocedure of Example 1.

EXAMPLE XXIX Preparation 0 f 1- (3-dimethylaminopropyl) -3-(m-trifluoromethylphenyl)-2-imidaz0lidinone hydrochloride The above compound,melting point -157 C., is obtained when 1 -(mtrifluoromethylphenyl)-2-imidazolidinone is substituted for1-(-m-chlor-ophenyl)-2-imidazolidinone in the procedure of Example I.

EXAMPLE XXX I Preparation of 1-(3-[4-(2-acetoxyethyl)piperazino1- propyl-3-(m-chl0r0phenyl -2imidazolidirz0ne A solution of 3 parts ofl-(m-chlorophenyl)-2-i midazolidinone in 30 parts of diglyme is addeddropwise to a slurry of 0.7 part of 50% sodium hydride (in mineral oil)in 50 parts of diglyme. The reaction mixture is stirred for one hour anda solution of 3.5 parts of 3-[4-(2-acetoxyethyDpiperazino]propylchloride in 20 parts of di glyme is added. The reaction mixture isheated at reflux temperature for 3 hours and then concentrated to removethe solvent. The residue is treated with dilute hydrochloric acid andthe aqueous mixture is extracted with ether to remove unreacted startingmaterial. The aqueous layer is cooled in an ice hath, made basic byaddition of dilute sodium hydroxide solution and extracted withchloroform. The desired compound is obtained by concentration of thechloroform layers.

EXAMPLE XXXI Preparation of 1- (m-chlorophenyl) -3- (3- [4-(2-hydr0xyethyl) pi perazino] propyl -2 -imi dazolidinone A mixture of 1 part of1-(3-[4-(2-acetoxyethyl)piperazino] propyl -3- m-chlorophenyl)-2-imidazolidinone. and 10 parts of 2 N ethanolic sodium hydroxide isheated at reflux temperature for 2 hours and concentrated. The residueis diluted Wtih 10 parts of Water and extracted with chloroform. Thedesired product is obtained'when the chloroform layer is concentrated.

7 EXAMPLE XXXII Preparation of 1 (m-chlorophenyl -3- (4-dimethylaminabutyl)-2-i1nidaz0lidinone hydrochloride The above compoundis'obtained when 4-dimethyl aminobutyl chloride is substituted for the3-dimethylaminopropyl chloride in the procedure of Example I.

9 EXAMPLE XXXIH Preparation of l-(m-chlorophenyl)-3-(2-propargylmethylamz'noethyl)-2-imidazolidinone hydrochloride Theabove compound is obtained when 2-propargylmethylaminoethyl chloride isSubstituted for 3-dimethyl- .aminopropyl chloride in the process ofExample I.

The above compound is obtained when Z-allylmethylaminoethyl chloride issubstituted for 3-dimethylaminopropyl chloride in the process of Example1.

EXAMPLE XXXV Preparation of 1- (m-chlorophenyl) -3-(2-cyclohexylmethylaminoethyl) -2 -im idozolidinone hydrochloride Theabove compound is obtained when Z-cyclohexylmethylaminoethyl chloride issubstituted for 3dimethylaminopropyl chloride in the process of ExampleI.

EXAMPLE XXXVI Preparation ofl-(m-acetylphenyl)-3-(S-dimethylaminopropyl)-2-imidazoliainonehydrochloride The above compound is obtained whenl-(m-acetylhenyD-Z-imidazolidinone .is substituted for the 1-(mchlorophenyn-2-imidazolidinone in the process of Example I.

EXAMPLE XXXVII Preparation of 1 m-bromophenyl) -3- (2-dimethylaminoethyl) -2-imidazolidinone hydrochloride A solution of 6.8parts of l-(m-bromophenyl)-2-imidazolidinone in 50 ml. of diglyme isadded dropwise to a slurry of 1.6 parts of 50% sodium hydride (inmineral oil) in 50 parts of diglyme. The reaction mixture is stirred forone hour and a solution of 3.8 parts of 2-dimethylaminoethyl chloride in150 parts of ether is added. The reaction mixture is stirred for onehour at room temperature. heated to remove the ether and heated atreflux temperature for 3 hours. The reaction mixture is filtered and themother liquor is concentrated to remove the solvent. The residue istriturated with l N hydrochloric acid and the mixture is extracted withether to remove unreacted starting material. The acid solution is madealkaline by addition of 5 N sodium hydroxide solution and then extractedWith ether. The ether extracts are dried over magnesium sulfate and thentreated with ethanolic hydrogen chloride. Thel-'(m-bromophenyl)-3-(Z-dimethylaminoethyl)-2imidazolidinonehydrochloride separates. It melts at 227-229 C. after recrystallization.

EXAMPLE XL Preparation of 1- (m-methoxyphenyl) -3-(Z-dimethylaminoethyl) 2-imidazolidirtone hydrochloride Whenl-(m-methoxyphenyl)-2-imidazolidinone is substituted forl-(m-bromophenyl)-2-imidazolidinone in the process of Example XXXVII,the above ing point 220-222 C., is obtained.

EXAMPLE XLI Preparation of J-(Z-dimethylarninoelhyl)-3-(mmethylthiophejzyl) 2-ir riidazolidirtlone hydrochloride The abovecompound, melting point 14 8 -150 C., is obtained whenl-(m-methylthiophenyl)-2-imidazolidinone is substituted forl-(m-bromophenyl)-2 imidazolidinone in the process of Example XXXVII.

EXAMPLE XLII Preparation of1-(imbenzyloxyphenyl)-3-(2-dimethylaminoethyl)-2-imidazolidinonehydrochloride The above compound is obtained whenl-(rn-benzyloxyphenyl)-2-imidazolidinone is substituted for 1- m-.bromophenyl)-2-imidazolidinone in the process of Example XXXVII.

EXAMPLE XLIII Preparation of 1- (3-dimethylamlzhopnopyl) -3-(m-methylsulfonylphcnyl) -2-imidaoolidinone hydnoch loride A mixture of1.65 par-ts of 1-(3-dimethylaminopropyl)-3-(m-methylthiophenyl)-2-irnidazolidinone, 1.3 parts of 30% hydrogenperoxide and 6 parts of acetic acid is heated in a steam bath for 2 /2hours. cooled and treated with 23 parts of 5 N sodium hydroxidesolution. The reaction mixture is extracted with chloroform and thechloroform layer is washed With Water and then concentrated to removethe solvent. The residue is dissolved in 3 parts of ethanol and 2.5parts of 1.8 N ethanolic hydrogen chloride is added. The mixture iscooled and the desired product is filtered and further purified byrecrystallization from ethanol.

EXAMPLE XLIV Preparation of 1- (m-hydroayphenyl) -3-(Z-a'imelhylomiiroethyl) -2-!imidozolidinonc hydrochloride ether.

EXAMPLE XLV Prepanalioiz of 1-(m-?iodophenyl)-3-(Z-dimethylaminoethyl)-2-imidaaolidinone hydrochloride The above compound is obtained whenl-(m-iodophenyl)2-imidazolidinone is substituted forl-(m-bromophenyl)-2-imidazolidinone in the procedure of EX- ampleXXXVII.

EXAMPLE XLVI Preparation of I (m-chlioroph enyl -3- [2- 3 ,5 -dimethylmorpholino) ethyl] -2-imidazolidinone hydrochloride The abovecompound is obtained when 2-(3,5-dimethylmorpholino)ethyl chloride issubstituted for 3-dimethylaminopropyl chloride in the procedure ofExample I.

EXAMPLE XLVII Prepahatiort of 1 (m-chlorophenyl) -3- (2-pyrrolidinloethyl) -2-imidazolidinethione A mixture of 3 parts of1-(m-ch1orophenyl)-3-(2 pyrrolidinoethyl) 2 imidazolidinonehydrochloride, 3 parts of phosphorus pentasulfide and 15 parts of xyleneis heated at reflux temperature for 28 hours. A mixture of 50 parts of 2N sodium hydroxide and 50 parts of compound, melt- Preparation of1-(m-chl0r0phenyl)-3-(Z-diethylaminioethyl)-2-imidaz|0lidineth$0nc Theabove compound is obtained whenl-(rn-chlorophenyl)-3-(2-diethylaminoethyl) -2 imidazolidinonehydrochloride is substituted for 1-(m-chlorophenyl)3-(2-pyrrolidinoethyl)-2-imidazolidinone in the process of Example XLVII.

1. A compound of the formulaz wherein R is a member of the groupconsisting of hydrogen, halogen, lower alkyl, lower allroxy,trifiuoromethyl, lower alkylthio, lower alkylsulfonyl, lower alkanoyl,hydroxy and benzyloxy groups; R and R are members of the groupconsisting of hydrogen, lower alkyl, lower alkenyl, propargyl,cycloalkyl less than 7 carbons and phenyl (lower)alkyl and when takentogether with the nitrogen form pyrrolidino, lower alkylpyrrolidino,piperidino, lower alkylpiperidino, hexamethyleneimino, morpholino, loweralkylmorpholino, lower alkylpiperazino, hydroxy-lower alkylpiperazinoand lower alltanoyloxy-lower alkylpiperazino groups; Y is a member ofthe group consisting of oxygen and sulfur; n is an integer from 2 to 4and A and B are member of the group consisting of hydrogen and loweralkyl groups and therapeutically useful salts thereof.

2. A compound according to claim 1 wherein R is halogen, R and R arelower allryl, A and B are hydrogen and n is 2. 7

a s2 3. A compound according to claim 1 wherein R is halogen ispyrrolidino and A and B are hydrogen.

4. The compound 1-(-chlorophenyl)-3(2-dimethylaminoethyl)-2-imidazolidinone.

S. The compound -1(m-chlorophenyl)-3-(2-ethylrnethylaminoethyl)-2-imidazolidinone.

6. The compound 1-(m-chlorophenyl)-3-(2-pyrrolidinoethyl-2-imidazolidinone.

7. The com ound 1-phenyl-3-(2-piperidinoethyl)-2-imidazolidinone.

is. The compound l-(m-chlorophenyl)-3-(2-piperidinoethyl)-2-imidazolidinone.

9. The compound 1-(2-benzylmethylaminoethyl)-3(mchlorophenyl-2-imidazolidinone.

it). The compound l-(2-pyrrolidinoethy1)-3-phenyl-2- imidazolidinone.

M. The compound 1 (2 ethylrnethylaminoethyl)-3-phenyl-Z-imidazolidinone.

12. The compound 1 (m-chlorophenyl)-3-(2-diethylaminoethyl-2-imidazolidinone.

13. The compound 1-phenyl-3-(Z-dimethylamihoethyl)- 2-imidazolidinone.

M. The compound l-(m-chlorophenyl)-3-(3-dimethylaminopropyl-2-imidazolidinone.

15. The compound l-(Z-diethylarninoethyl)-3-phenyl- Z-imidazolidinone.

16. The compound1-(m-chlorophenyl)-3-(2-rnorphoinoethyl)-2-imidazolidinone.

17. The compound 1-(m-bromophenyl)-3-(2-dimethylaminoethyl-2-imidazolidinone.

13. The compound 1-(in-chlorophenyl)-3-(2-pyrrolidinoethyl)-2-irnidazolidinethione.

19. The compound 1- (m-chlorophenyl)-3-(2-diethylaminoethyl)-2-imirlazolidinethione.

References Cited by the Examiner Elderfield, Heterocyclic Compounds,vol. 5, page 261, John Wiley and Sons, Inc, New York (1957).

Hofmann, The Chemistry of Heterocyclic Compounds, Imidazole and ItsDerivatives, part 1, pp. 226 227, Interscience Publishers, The, New York(1953).

NICHOLAS S. RIZZO, Primary Examiner.

l. MARCUS, Examiner.

1. A COMPOUND OF THE FORMULA:
 16. THE COMPOUND1-(M-CHLOROPHENYL)-3-(2-MORPHOLINOETHYL)-2-IMIDAZOLIDINONE.